The purpose of this proposed study is to test the utility of the micronucleus assay as a marker of cytogenetic damage to the bronchial epithelium in a population occupationally exposed to radon daughters. This technique is a promising new tool for cancer epidemiology; it appears to be sensitive to known carcinogens including ionizing radiation and tobacco products, and gives a measure of cellular response to exposure in the intact organism. When adapted to exfoliatied cells, the micronucleus assay can be conducted on samples of tissues where common tumors form (such as bronchi, uterine cervix and mouth) which are easily obtainable with minimally invasive procedures. This investigation will utilize historical sputum specimens and data on occupational history, smoking, and other factors from workers employed in underground and open-pit uranium mines and uranium mills in the Colorado Plateau between 1960 and 1980 The incidence of bronchogenic cancer is markedly elevated in underground miners. Inhaled radon daughters are regarded as the cause of excess lung cancer among these workers. The availability of biological materials, data on exposures and potential confounders, and information on disease occurrence from this population present a valuable opportunity for a variety of epidemiologic studies involving biochemical markers of effect. The primary hypothesis to be tested by this study is that the proportion of micronucleated bronchial squamous cells is increased in underground uranium miners occupationally exposed to radon daughters, compared to unexposed workers. The occurrence of micronuclei is expected to be related to radon-daughter dose. The study will be conducted in two phases. In the first phase, laboratory procedures will be developed, personnel will be trained in scoring micronuclei, and background proportions of micronucleated cells will be determined. In the second phase, the micronucleus assay will be performed on exfoliated bronchial cells in sputum from uranium workers, and these data will be analyzed with regard to radon-daughter exposure, smoking, and other factors to test the study hypotheses. Finding an association between the occurrence of micronuclei and radon-daughter exposure in this study would justify future research to test the micronucleus assay in the large population which is exposed to radon daughters in private dwellings and to further examine the relationships among exposure, mcironuclei, and cancer in miners.